Full Text Journal Articles by
Author Klaus Buchner

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Natalizumab treatment shows low cumulative probabilities of confirmed disability worsening to EDSS milestones in the long-term setting.

Maria Trojano, Helmut Butzkueven, Ludwig Kappos, Heinz Wiendl, Tim Spelman, Fabio Pellegrini, Yi Chen, Qunming Dong, Harold Koendgen, Shibeshih Belachew, ,

BACKGROUND:Though the Expanded Disability Status Scale (EDSS) is commonly used to assess disability level in relapsing-remitting multiple sclerosis (RRMS), the criteria defining disability progression are used for patients with a wide range of baseline levels of disability in relatively short-term trials. As a result, not all EDSS changes carry the ... Read more >>

Mult Scler Relat Disord (Multiple sclerosis and related disorders)
[2018, 24:11-19]

Cited: 1 time

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SDF-1 inhibition targets the bone marrow niche for cancer therapy.

Aldo M Roccaro, Antonio Sacco, Werner G Purschke, Michele Moschetta, Klaus Buchner, Christian Maasch, Dirk Zboralski, Stefan Zöllner, Stefan Vonhoff, Yuji Mishima, Patricia Maiso, Michaela R Reagan, Silvia Lonardi, Marco Ungari, Fabio Facchetti, Dirk Eulberg, Anna Kruschinski, Axel Vater, Giuseppe Rossi, Sven Klussmann, Irene M Ghobrial,

Bone marrow (BM) metastasis remains one of the main causes of death associated with solid tumors as well as multiple myeloma (MM). Targeting the BM niche to prevent or modulate metastasis has not been successful to date. Here, we show that stromal cell-derived factor-1 (SDF-1/CXCL12) is highly expressed in active ... Read more >>

Cell Rep (Cell reports)
[2014, 9(1):118-128]

Cited: 40 times

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Crystal structure of a mirror-image L-RNA aptamer (Spiegelmer) in complex with the natural L-protein target CCL2.

Dominik Oberthür, John Achenbach, Azat Gabdulkhakov, Klaus Buchner, Christian Maasch, Sven Falke, Dirk Rehders, Sven Klussmann, Christian Betzel,

We report the crystal structure of a 40 mer mirror-image RNA oligonucleotide completely built from nucleotides of the non-natural L-chirality in complex with the pro-inflammatory chemokine L-CLL2 (monocyte chemoattractant protein-1), a natural protein composed of regular L-amino acids. The L-oligonucleotide is an L-aptamer (a Spiegelmer) identified to bind L-CCL2 with ... Read more >>

Nat Commun (Nature communications)
[2015, 6:6923]

Cited: 28 times

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Identification and characterization of a mirror-image oligonucleotide that binds and neutralizes sphingosine 1-phosphate, a central mediator of angiogenesis.

Werner G Purschke, Kai Hoehlig, Klaus Buchner, Dirk Zboralski, Frank Schwoebel, Axel Vater, Sven Klussmann,

The sphingolipid S1P (sphingosine 1-phosphate) is known to be involved in a number of pathophysiological conditions such as cancer, autoimmune diseases and fibrosis. It acts extracellularly through a set of five G-protein-coupled receptors, but its intracellular actions are also well documented. Employing in vitro selection techniques, we identified an L-aptamer (Spiegelmer®) ... Read more >>

Biochem. J. (The Biochemical journal)
[2014, 462(1):153-162]

Cited: 9 times

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A mixed mirror-image DNA/RNA aptamer inhibits glucagon and acutely improves glucose tolerance in models of type 1 and type 2 diabetes.

Axel Vater, Simone Sell, Przemyslaw Kaczmarek, Christian Maasch, Klaus Buchner, Ewa Pruszynska-Oszmalek, Pawel Kolodziejski, Werner G Purschke, Krzysztof W Nowak, Mathias Z Strowski, Sven Klussmann,

Excessive secretion of glucagon, a functional insulin antagonist, significantly contributes to hyperglycemia in type 1 and type 2 diabetes. Accordingly, immunoneutralization of glucagon or genetic deletion of the glucagon receptor improved glucose homeostasis in animal models of diabetes. Despite this strong evidence, agents that selectively interfere with endogenous glucagon have ... Read more >>

J. Biol. Chem. (The Journal of biological chemistry)
[2013, 288(29):21136-21147]

Cited: 29 times

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The effects of the anti-hepcidin Spiegelmer NOX-H94 on inflammation-induced anemia in cynomolgus monkeys.

Frank Schwoebel, Lucas T van Eijk, Dirk Zboralski, Simone Sell, Klaus Buchner, Christian Maasch, Werner G Purschke, Martin Humphrey, Stefan Zöllner, Dirk Eulberg, Frank Morich, Peter Pickkers, Sven Klussmann,

Anemia of chronic inflammation is the most prevalent form of anemia in hospitalized patients. A hallmark of this disease is the intracellular sequestration of iron. This is a consequence of hepcidin-induced internalization and subsequent degradation of ferroportin, the hepcidin receptor and only known iron-export protein. This study describes the characterization ... Read more >>

Blood (Blood)
[2013, 121(12):2311-2315]

Cited: 62 times

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Polyetheylenimine-polyplexes of Spiegelmer NOX-A50 directed against intracellular high mobility group protein A1 (HMGA1) reduce tumor growth in vivo.

Christian Maasch, Axel Vater, Klaus Buchner, Werner G Purschke, Dirk Eulberg, Stefan Vonhoff, Sven Klussmann,

High mobility group A1 (HMGA1) proteins belong to a group of architectural transcription factors that are overexpressed in a range of human malignancies, including pancreatic adenocarcinoma. They promote anchorage-independent growth and epithelial-mesenchymal transition and are therefore suggested as potential therapeutic targets. Employing in vitro selection techniques against a chosen fragment ... Read more >>

J. Biol. Chem. (The Journal of biological chemistry)
[2010, 285(51):40012-40018]

Cited: 18 times

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SDF-I binding nucleic acids

WERNER PURSCHKE, FLORIAN JAROSCH, DIRK EULBERG, SVEN KLUSSAMANN, KLAUS BUCHNER, CHRISTIAN MAASCH, NICOLE DINSE,

The present invention is related to a nucleic acid molecule, preferably binding to SDF-I, selected from the group comprising type A nucleic acid molecules, type B nucleic acid molecules, type C nucleic acid molecules and nucleic acid molecules having a nucleic acid sequence according to any of SEQ.ID.No. 142, SEQ.ID.No. ... Read more >>

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Late onset of Ccl2 blockade with the Spiegelmer mNOX-E36-3'PEG prevents glomerulosclerosis and improves glomerular filtration rate in db/db mice.

Volha Ninichuk, Sebastian Clauss, Onkar Kulkarni, Holger Schmid, Stephan Segerer, Ewa Radomska, Dirk Eulberg, Klaus Buchner, Norma Selve, Sven Klussmann, Hans-Joachim Anders,

Diabetic kidney disease is associated with monocyte chemoattractant CC chemokine ligand 2 (CCL2)-dependent glomerular and interstitial macrophage recruitment. In addition, nephropathy is delayed in Ccl2 mutant diabetic mice. However, whether the late onset of therapeutic Ccl2 blockade modulates the progression of advanced diabetic nephropathy remains unknown. We addressed this question ... Read more >>

Am. J. Pathol. (The American journal of pathology)
[2008, 172(3):628-637]

Cited: 66 times

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Physicochemical stability of NOX-E36, a 40mer L-RNA (Spiegelmer) for therapeutic applications.

Christian Maasch, Klaus Buchner, Dirk Eulberg, Stefan Vonhoff, Sven Klussmann,

Spiegelmers are structured mirror-image oligonucleotides that are designed to bind and inhibit pharmacologically relevant target molecules. The synthesis and purification of mirror-image oligonucleotides is comparable to the manufacturing of standard oligonucleotides that consist of naturally configured nucleotides. Due to the use of the non-natural L-nucleotides in Spiegelmers, these oligonucleotides show ... Read more >>

Nucleic Acids Symp Ser (Oxf) (Nucleic acids symposium series (2004))
[2008, (52):61-62]

Cited: 7 times

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In vitro selection using a dual RNA library that allows primerless selection.

Florian Jarosch, Klaus Buchner, Sven Klussmann,

High affinity target-binding aptamers are identified from random oligonucleotide libraries by an in vitro selection process called Systematic Evolution of Ligands by EXponential enrichment (SELEX). Since the SELEX process includes a PCR amplification step the randomized region of the oligonucleotide libraries need to be flanked by two fixed primer binding ... Read more >>

Nucleic Acids Res. (Nucleic acids research)
[2006, 34(12):e86]

Cited: 32 times

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Novel use of enantiomer

FLORIAN JAROSCH, CHRISTIAN MAASCH, SVEN KLUSSMANN, AXEL VATER, DIRK EULBERG, WERNER PURSCHKE, KLAUS BUCHNER,

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Spiegelmer inhibition of CCL2/MCP-1 ameliorates lupus nephritis in MRL-(Fas)lpr mice.

Onkar Kulkarni, Rahul D Pawar, Werner Purschke, Dirk Eulberg, Norma Selve, Klaus Buchner, Volha Ninichuk, Stephan Segerer, Volker Vielhauer, Sven Klussmann, Hans-Joachim Anders,

The monocyte chemoattractant protein CCL2 is crucial for monocyte and T cell recruitment from the vascular to the extravascular compartment at sites of inflammation. CCL2 is expressed in human lupus nephritis and was shown to mediate experimental lupus; therefore, CCL2 antagonists may be beneficial for therapy. This study describes the ... Read more >>

J. Am. Soc. Nephrol. (Journal of the American Society of Nephrology : JASN)
[2007, 18(8):2350-2358]

Cited: 90 times

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MCP-1 binding nucleic acids

WERNER PURSCHKE, FLORIAN JAROSCH, DIRK EULBERG, SVEN KLUSSMANN, KLAUS BUCHNER, CHRISTIAN MAASCH,

The present invention is related to a nucleic acid, preferably binding to MCP-I, selected from the group comprising type IA nucleic acids, type IB nucleic acids, type 2 nucleic acids, type 3 nucleic acids, type 4 nucleic acids and nucleic acids having a nucleic acid sequence according to any of ... Read more >>

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Nucleic acids specifically binding bioactive ghrelin

SVEN KLUSSMANN, STEFFEN HELMLING, DIRK EULBERG, CHRISTIAN MAASCH, KLAUS BUCHNER,

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An L-RNA-based aquaretic agent that inhibits vasopressin in vivo.

Werner G Purschke, Dirk Eulberg, Klaus Buchner, Stefan Vonhoff, Sven Klussmann,

A class of diuretic/aquaretic agents based on mirror-image oligonucleotides (so-called Spiegelmers) has been identified. These molecules directly bind and inhibit the neuropeptide vasopressin (AVP). AVP is the major regulatory component of body fluid homeostasis mediated through binding to the renal V(2) receptor. Elevated plasma levels of AVP are implicated in ... Read more >>

Proc. Natl. Acad. Sci. U.S.A. (Proceedings of the National Academy of Sciences of the United States of America)
[2006, 103(13):5173-5178]

Cited: 20 times

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Inhibition of ghrelin action in vitro and in vivo by an RNA-Spiegelmer.

Steffen Helmling, Christian Maasch, Dirk Eulberg, Klaus Buchner, Werner Schröder, Christian Lange, Stefan Vonhoff, Britta Wlotzka, Matthias H Tschöp, Stefan Rosewicz, Sven Klussmann,

Employing in vitro selection techniques, we have generated biostable RNA-based compounds, so-called Spiegelmers, that specifically bind n-octanoyl ghrelin, the recently discovered endogenous ligand for the type 1a growth hormone secretagogue (GHS) receptor. Ghrelin is a potent stimulant of growth hormone release, food intake, and adiposity. We demonstrate that our lead ... Read more >>

Proc. Natl. Acad. Sci. U.S.A. (Proceedings of the National Academy of Sciences of the United States of America)
[2004, 101(36):13174-13179]

Cited: 65 times

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Short bioactive Spiegelmers to migraine-associated calcitonin gene-related peptide rapidly identified by a novel approach: tailored-SELEX.

Axel Vater, Florian Jarosch, Klaus Buchner, Sven Klussmann,

We developed an integrated method to identify aptamers with only 10 fixed nucleotides through ligation and removal of primer binding sites within the systematic evolution of ligands by exponential enrichment (SELEX) process. This Tailored-SELEX approach was validated by identifying a Spiegelmer ('mirror-image aptamer') that inhibits the action of the migraine-associated ... Read more >>

Nucleic Acids Res. (Nucleic Acids Research)
[2003, 31(21):e130]

Cited: 67 times

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